SETDB1 mediated FosB expression increases the cell proliferation rate during anticancer drug therapy

Abstract

The efficacy of anticancer drugs depends on a variety of signaling pathways, which can be positively or negatively regulated. In this study, we show that SETDB1 HMTase is down-regulated at the transcriptional level by several anticancer drugs, due to its inherent instability. Using RNA sequence analysis, we identified FosB as being regulated by SETDB1 during anticancer drug therapy. FosB expression was increased by treatment with doxorubicin, taxol and siSETDB1. Moreover, FosB was associated with an increased rate of proliferation. Combinatory transfection of siFosB and siSETDB1 was slightly increased compared to transfection of siFosB. Furthermore, FosB was regulated by multiple kinase pathways. ChIP analysis showed that SETDB1 and H3K9me3 interact with a specific region of the FosB promoter. These results suggest that SETDB1-mediated FosB expression is a common molecular phenomenon, and might be a novel pathway responsible for the increase in cell proliferation that frequently occurs during anticancer drug therapy. [BMB Reports 2016; 49(4): 238-243]

Enhanced expression of SETDB1 possesses prognostic value and promotes cell proliferation, migration and invasion in nasopharyngeal carcinoma

“…Recent studies indicate that SETDB1 is markedly increased in various types of human cancer, including melanoma, lung cancer, hepatocellular carcinoma, breast, urothelial carcinoma and prostate cancer, contributing to enhanced tumor growth and metastasis. Hence, SETDB1 is a promising therapeutic target for cancer (39)(40)(41). This study furthered the understanding of SETDB1 and explored its potential role in tumorigenesis and NPC.…”

Bach2 represses the AP-1-driven induction of interleukin-2 gene transcription in CD4+ T cells

“…Twenty-four hours after transfection, live cells were cultured for 24 hours with or without PMA/ionomycin, and assayed with a Luciferase Assay System (Promega) according to the manufacturer’s protocol. Firefly luciferase activity was normalized to either β-galactosidase activity or Renilla luciferase activity and recorded as relative luciferase units (RLUs) ( 26 ).…”

Knockdown of SET Domain, Bifurcated 1 suppresses head and neck cancer cell viability and wound-healing ability in vitro

“…There was no significant decrease in cell viability in carcinoma cells, but Wu et al reported that SETDB1 expression in metastatic lung cancer cells is low and inhibits cell migration by inhibiting the polymerization of actin (Wu et al, 2014). According to Na et al, SETDB1 knockdown increased cell viability in lung cancer (Na et al, 2016). The effect of SETDB1 knockdown may be different according to the type of cancer and may play a more critical role in the cancer's progression.…”

“…The MTT assay (3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) (Sigma-Aldrich, Germany) was used to evaluate the effect of SETDB1 on cell viability (Na et al, 2016). MTT was dissolved in DPBS (GE Healthcare, USA).…”